Sodium Bicarbonate → 3-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1929977Notes

Reaction equation

HRID 1929977 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:24][CH2:23][CH2:22][N:12]2[C:13]=1[C:14]1[N:15]=[N:16][C:17]([NH:20][NH2:21])=[CH:18][CH:19]=1.[Si:25]([O:32][CH2:33][C:34]([CH3:38])([CH3:37])[CH:35]=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:25]([O:32][CH2:33][C:34]([C:38]1[N:16]2[N:15]=[C:14]([C:13]3[N:12]4[CH2:22][CH2:23][CH2:24][C:11]4=[N:10][C:9]=3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:19]=[CH:18][C:17]2=[N:20][N:21]=1)([CH3:37])[CH3:35])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 106563753-((Tert-butyldimethylsilyl)oxy)-2,2-dimethylpropanalHCID 12217721Iodo benzene diacetateHCID 579298742-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

Product 1

HCID 579299783-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazineYield 90.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (6.00 g, 18.3 mmol, Example #35, Step E) was suspended in DCM (125 μL) then 3-(tert-butyldimethylsilyloxy)-2,2-dimethylpropanal (4.15 g, 19.2 mmol, J. Org. Chem., 2002, 67, 2474-2480) was added. The mixture was stirred at ambient temperature for about 2 h. Iodobenzene diacetate (6.00 g, 18.6 mmol) was added then the mixture was stirred for about 30 min. Saturated aqueous NaHCO3 (150 mL) was added then the layers were separated. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The material was purified by flash chromatography on silica gel with EtOAc as an eluent to give the title compound (8.67 g, 90%): LC/MS (Table 1, Method g) Rt=2.77 min; MS m/z: 525.3.2 (M+H)+.

Workup

  1. stirringthe mixture was stirred for about 30 min
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified by flash chromatography on silica gel with EtOAc as an eluent

Sources & evidence

ORD record
ord-dc01374e1f6a42bfb7a30abde210f0fa
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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